TITLE:
Liquid Chromatography-Tandem Mass Spectrometry Methods for Determination of Delamanid in Mouse Plasma and Lung
AUTHORS:
Yukihiro Hirao, Toshihisa Koga, Noriyuki Koyama, Yoshihiko Shimokawa, Ken Umehara
KEYWORDS:
Delamanid, LC-MS/MS, Mouse Plasma, Mouse Lung, Pharmacokinetics
JOURNAL NAME:
American Journal of Analytical Chemistry,
Vol.6 No.2,
January
16,
2015
ABSTRACT: Sensitive
and selective liquid chromatography-tandem mass spectrometry methods have been
developed and validated for the determination of delamanid in mouse plasma and
lung. Sample preparation involved liquid-liquid extraction with diethyl ether
for plasma, or protein precipitation followed by liquid-liquid extraction with tert-butyl methyl ether for lung
homogenate. Chromatographic separation was performed on a reversed phase column
with a linear gradient elution using purified water-formic acid (1000:2, v/v)
and methanol-formic acid (1000:2, v/v) at a flow rate of 0.2 mL/min. Detection
was performed on a triple-quadrupole tandem mass spectrometer using positive
ion electrospray ionization in the selected reaction monitoring mode. The
analytical methods were successfully validated for selectivity, calibration
curve, accuracy, precision, extraction recovery, and stability over a range of
6 - 1000 ng/mL for plasma and 10 - 1000 ng/mL for lung homogenate. The
validated methods were successfully applied for evaluation of pharmacokinetics
of delamanid in male mice.